TY - JOUR
T1 - Omega-6 fatty acid biomarkers and incident type 2 diabetes
T2 - pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies
AU - Wu, Jason H.Y.
AU - Marklund, Matti
AU - Imamura, Fumiaki
AU - Tintle, Nathan
AU - Ardisson Korat, Andres V.
AU - de Goede, Janette
AU - Zhou, Xia
AU - Yang, Wei Sin
AU - de Oliveira Otto, Marcia C.
AU - Kröger, Janine
AU - Qureshi, Waqas
AU - Virtanen, Jyrki K.
AU - Bassett, Julie K.
AU - Frazier-Wood, Alexis C.
AU - Lankinen, Maria
AU - Murphy, Rachel A.
AU - Rajaobelina, Kalina
AU - Del Gobbo, Liana C.
AU - Forouhi, Nita G.
AU - Luben, Robert
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Kalsbeek, Anya
AU - Veenstra, Jenna
AU - Luo, Juhua
AU - Hu, Frank B.
AU - Lin, Hung Ju
AU - Siscovick, David S.
AU - Boeing, Heiner
AU - Chen, Tzu An
AU - Steffen, Brian
AU - Steffen, Lyn M.
AU - Hodge, Allison
AU - Eriksdottir, Gudny
AU - Smith, Albert V.
AU - Gudnason, Vilmunder
AU - Harris, Tamara B.
AU - Brouwer, Ingeborg A.
AU - Berr, Claudine
AU - Helmer, Catherine
AU - Samieri, Cecilia
AU - Laakso, Markku
AU - Tsai, Michael Y.
AU - Giles, Graham G.
AU - Nurmi, Tarja
AU - Wagenknecht, Lynne
AU - Schulze, Matthias B.
AU - Lemaitre, Rozenn N.
AU - Chien, Kuo Liong
AU - Soedamah-Muthu, Sabita S.
AU - Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/12
Y1 - 2017/12
N2 - Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49–76 years with a BMI (range of cohort means) of 23·3–28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60–0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88–1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funding Funders are shown in the appendix.
AB - Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49–76 years with a BMI (range of cohort means) of 23·3–28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60–0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88–1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funding Funders are shown in the appendix.
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U2 - 10.1016/S2213-8587(17)30307-8
DO - 10.1016/S2213-8587(17)30307-8
M3 - Article
C2 - 29032079
AN - SCOPUS:85031309422
SN - 2213-8587
VL - 5
SP - 965
EP - 974
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 12
ER -
